The following is mostly mouse science... sorry. Need human translation.

To make supernumerary ovaries in mice, you'd have to re-create the conditions that normally produce one ovary per side, do it in an extra location, and then make sure germ cells and ducts/niche follow suit.

What an ectopic ovary needs

  1. A second gonadal primordium (genital ridge) in the coelomic epithelium. The ridge forms when the coelomic epithelium thickens and turns on a core program (GATA4 - LHX9/WT1 - NR5A1/SF1). GATA4 activity sweeps A-P and is required to initiate ridge formation; LHX9 and WT1 are also essential for early ridge growth/identity. PMC

  2. Ovarian fate within that primordium. Once a ridge exists, ovarian specification depends on RSPO1-WNT4-beta-catenin signaling (antagonizing the testis pathway). PMC

  3. A way to capture migrating PGCs. Primordial germ cells home to the ridge via CXCL12-CXCR4 chemotaxis, KITL-KIT trophic support, and beta1-integrin-mediated adhesion; without these, colonization is inefficient. An ectopic site must present the same cues. PubMed

  4. Integration with ducts/mesentery for morphogenesis. Normal ovary encapsulation and final shape depend on coordinated movements with the mesonephric ducts/oviduct; the oviduct is required for ovary encapsulation. A supernumerary ovary will need analogous Mullerian tissue nearby. PMC

Strategy (with timing)

Step 1 -- Induce a second genital ridge (E9.25-E10.5)
  • Strategy: Create a new, localized domain of the ridge-initiating program in coelomic epithelium.
  • How: A short dose of GATA4 (and/or WT1/LHX9) in mesothelium overlying the mesonephros, offset from the native ridge (e.g., Wt1-CreERT2 or Msln-Cre driving a Rosa26LSL-GATA4 cassette), while ensuring NR5A1/SF1 can turn on downstream. GATA4 is upstream of ridge thickening; LHX9/WT1 help activate SF1 and sustain AGP/UGR identity. PMC
  • Guardrails: Keep expression spatially tight and time-boxed (E9.25-E10.0). Overbroad SF1 can cause ectopic adrenal-like tissue, so the sequence should be GATA4/LHX9/WT1 first, then permit endogenous SF1 to rise, not pan-mesothelial SF1 overexpression. PMC
Step 2 -- Lock ovarian identity in the new ridge (E11.0-E12.5)
  • Strategy: Bias supporting cells toward granulosa fate.
  • How: In the ectopic ridge, drive RSPO1 or stabilize beta-catenin (e.g., Rspo1tetO + ridge-restricted tTA; or Ctnnb1ex3 with very tight mosaic activation). Pair with FOXL2 up-tuning to reinforce ovarian identity. RSPO1-WNT4-beta-catenin is the core pro-ovary axis. PubMed
Step 3 -- Ensure PGC capture to both native and ectopic sites (E9.5-E11.5)
  • Strategy: Build a second chemokine/trophic sink on the peritoneal surface over the new ridge.
  • How: Ectopically express CXCL12 and KITL in mesothelium/underlying mesenchyme flanking the ectopic ridge, and mildly raise CXCR4 in PGCs (PRDM1- or DDX4-driven). Support adhesion via ECM and beta1-integrin competence.
  • Why: CXCL12-CXCR4, KITL-KIT gradients and beta1-integrin are required for efficient gonadal colonization. PubMed
Step 4 -- Provide ductal/mesenteric context so the organ can morph correctly (E12.5-birth)
  • Strategy: Bring a Mullerian duct/oviduct segment into proximity with the ectopic ridge.
  • Method 1: Duplicate/branch the Mullerian tip locally by enhancing WNT9B signaling from adjacent Wolffian duct epithelium and/or GATA3 in Wolffian duct, which guide Mullerian elongation; or reposition the ridge near existing duct. PMC
  • Method 2: Exploit the normal coupling between gonad + ducts (they move together in 3D) to favor encapsulation of the ectopic ovary; oviduct is needed for encapsulation. PMC
Step 5 -- Scale the somatic niche and assembly (E14.5-P3)
  • Strategy: Ensure enough pregranulosa cells to enclose oocytes.
  • How: Brief, ridge-restricted RSPO1/WNT expression boost to expand LGR5+ pregranulosa progenitors; keep Notch in its normal window to promote cyst resolution and single-oocyte follicles. (Somatic scaling is necessary so the new ovary isn't a germ-cell-rich but follicle-poor rudiment.) PMC

Practical considerations for making an extra ovary

  • Can we make any extra ridge? Since GATA4 loss abolishes ridge initiation, the reciprocal (localized gain) is the most rational sufficiency test; pair with LHX9/WT1 to stabilize identity and allow endogenous SF1 to rise. PMC
  • PGCs are limiting and follow cues. If you make two ridges, one may steal PGCs. You likely need more PGCs upstream (e.g., brief BMP-PRDM1/14 push) or stronger CXCL12/KITL at both sites so neither ovary is starved. PubMed
  • Avoid ectopic adrenal/testis programs. Broad NR5A1 overexpression can create adrenal-like tissue; keep SF1 under endogenous control. Enforce RSPO1-WNT4-beta-catenin and FOXL2 to block SOX9 if any XY/testis drift occurs. ScienceDirect
  • Anatomy matters. The ovary's final architecture depends on coordinated movement with the mesonephric ducts and the oviduct; without nearby Mullerian tissue, the extra ovary may not encapsulate or vascularize properly. PMC
  • "Accessory/supernumerary ovaries" are described clinically in humans (sometimes far from the pelvis), proving the concept is developmentally plausible. Quantitative Imaging

Minimal build of an extra ovary strategy

  1. Ectopic ridge: transient GATA4 (+/- LHX9/WT1) activation in a discrete second patch of coelomic epithelium. PMC
  2. Ovarian fate: local RSPO1/beta-catenin activation + FOXL2 support. PubMed
  3. PGC capture: CXCL12 + KITL expression around the ectopic site. PubMed
  4. Mullerian proximity: mild WNT9B/GATA3 boost in adjacent Wolffian duct to bring an oviductal segment alongside the new ridge (or place the ridge close to the native duct). PMC

Surgical approaches

Some of the above genetic programs might be replaceable through surgical technique instead of genetic programs. These are just ideas and not validated.

  • surgical creation of a second ridge
  • direct physical capture of PGCs to the new site without chemotaxis
  • bring a piece of Müllerian duct to the graft so the supernumerary ovary becomes encapsulated